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Ken Mills, Ph.D., Principal Investigator

Class of 2026:

• Fiona Doherty, Chemistry 

• Alanna Mahar, Chemistry 

• Cristina Pedorella, Chemistry 

• Kyleigh Waggett, Chemistry/Biochem 

Class of 2027:

• Danielle Fiordaliso, Biology 

• Maria Pena Garcia, Chemistry  

• Ilan Guerrero, Chemistry/Biochem  

• Katrin White, Biology  

Class of 2028:

• Nana Akyeampong

• Mari Arias

Seelos STEM Scholar Alumni:

• Gia Ciaravino, Biology 2026

• Kiara Fontes, Math 2026

2025

• Libby Nompleggi, Chemistry 

• Emma Proffitt, Chemistry

• Caroline Quinn, Chemistry, PhD Student, Pittsburgh

• Cyndie Alexis, Health Studies, Nursing Student, Johnson and Wales

• Maria Campos, Chemistry

• Brynn Dundon, Chemistry

• Maggie O'Dea, Chemistry 

2024

• Sarah Carter, Biology/Biochem, PhD Student, Dartmouth

• Lilly Feeney, Chemistry 2024, CMA (Pre Med)

• Lily Nguyen, Chemistry 2024, Dental Assistant (Pre-Dental)

• Kallie Poon, Biology 2024, Jesuit Volunteer Corps (Pre-Med)

• Megan Yurchick, Chemistry 2024, Americorps (Pre-Med)

2023

• Josue Alvarado, FRAP/Sociology 

• Bea Barbesino, Chem, MD Student, Albany Medical College

• Michelle Haigbea, Bio/Honors, Pharmacy student, MCPHS

2022

• Justin Hackshaw, FRAP/Economics 

• Anthony D'Angelo, Chem, CRC Dana Farber

• Thuy Nguyen, Chem, Medical Student, University of Houston

• Lily Russo, Chem, Chemist, Chartpak

• Diana Wall, Bio, PhD student, Brown

2021

• Angel Chavez, Chemistry, Pfizer

• Bella Jankowski, Chem/Biochem, PhD student, UMass

• Liam Lewis, Chem, Teaching

• Mercedes Ruiz, English, Maxim Healthcare recruiter

• Sean Tarrant, Bio/Biochem, MD Student, Loyola Chicago

• Vaish Yalala, Chemistry, MD Student, UMass

2020

• Alexandra Cawood, Chem/Biochem, DO Student, W. Virginia SOM

• Chinnel Hudson, FRAP/Sociology, National Grid (PM)

2019

• Owen Conroy, Biology, Broad Institute

• Patrick Exconde, Chem/Biochem, PhD student UPenn

• Abby Lynch, Biology/Biochem, Research Assistant Duke

• Nhi Tran, UMass Amherst

• Amanda Wibben, Biology Fulbright India, MS Theology Harvard, MD Student Georgetown

2018

• Hannah Comeau, Chemistry, Masters, Johns Hopkins, Dana Farber

• Vanessa Costa, Sociology, Clinical specialist

• C.J. Janton, Bio/Biochem, DO/PhD student, NYIT

• Christian Ramsoomair, Chem/Biochem MD/PhD student, Miami

• Deirdre Reidy, Biology, MD, UConn

2017

• Shirley Amunya, Fitchburg St, Teach for America

• Alexander Bonano, Spanish, MPH, Tufts

• Josh Long, Biology, MD, SUNY Upstate 

• Chris Minteer, Chem/Biochem PhD, Yale

• Wanlin Zhang, Chem/Biochem, DDS, Touro

2016

• Chris Cousin, Chemistry, PharmD, MCPHS

• Julliard del Rosario, Cornell U

• Mike Koulopoulos, Chem/Biochem, MD Wake Forest

• Anthony Yakely, Chem/Biochem, JVC Northwest, MPH Yale

2015

• Dawilmer Castillo, Bridgewater St., Masters, Brown, Pharmacist

• Zach Giaccone, Chem/Biochem, DDS, UConn

• Mario Jaramillo, Biology, MD, Albany Med

• Isabelle Pierre, UMass Dartmouth

• Nikki Siegart, Bio/Biochem, MD SUNY Downstate

2014

• Sarah Cahn, Chemistry, Takeda Oncology

• Dan Haley, Chemistry DDS, UConn

2013

• Katie Colelli Chiarolanzio, Bio/Biochem, M.D., UVM

• Nick Gulbrandsen, Bio Fitchburg

• Michael Nicastri, Chem/Biochem PhD, UPenn, PD Columbia

• Jen Pusztay, Chem/Biochem , D.O. UNECOM

• Laura Urbanski , Chem/Biochem MD/PhD, UConn

• Jennie Williams, Chemistry , Program Director, Lovelane Riding

2012

• Stacy Chin, Chemistry, PhD, Boston U

• Kevin Karanja, Chemistry WSU, Autism Therapeutics Resources

• George Savidis, Bio/Biochem, Cytivia

   

2011

• Colleen Donahue, Biology, M.D., Tufts

• Michelle Marieni, Biology, M.D., Creighton

• Kevin O’Brien, Bio/Biochem PhD, U. Georgia, PD UMass Med

• Kristina Xega, Chemistry, MS Harvard, Takeda

2010

• Lauren Duffee, Bio/Biochem, D.V.M., UPenn

• Adam Nadelson, Biology, M.D., UMass

• Dan York, Bio/Biochem, MD, Texas Tech

2009

• Adam Kerrigan, Biology, Menlo Security

• Annie Schufreider, Chemistry, M.D., Loyola Chicago

• Jen Winslow, Biology, DO, University of New England

2008

• Melissa McGill, Bio/Biochem, M.S., Michigan, Pfizer

• Kathryn O’Brien, Chem/Biochem PhD, Cornell-Weill

2007

• Matt Drago, Bio/Biochem, M.D., UPenn

• Taryn Powers Surabian, Biology Bancroft School

2006

• Deirdre Dorval Wells, Biology J.D., Harvard Law School

2005

• Katie Lewandowski Bagnowski, Bio/Biochem PhD, Wash. U., PD Northwestern

2004

• Kate Leahy, Math, MD, Boston U

• Jackie Gareau Merrick, Chem/Biochem, Ph.D, Cornell-Weill

• Tim Quinn, Chem/Biochem, M.D.-Georgetown

2003

• Jenny Manning Chapnick, Biology

• Lisa Wuerdeman Lucas, Chemistry D.O., U. New England

• Ralph Millilo, Bio/Biochem, M.D. SUNY Upstate

• Lisa Garcia Seals, Biology Middle School Teacher

2002

• Beth Ambrose Dean, Chemistry Physician Assistant

• Pat Twomey, Chem/Biochem, M.D., Georgetown

• Kate Connor, Research Assistant

• Alvin Gomez, Research Associate 

• Julie Reitter, Ph.D., Research Associate

(Undergraduate co-authors indicated by asterisk)

40. *Yalala, V.R., *Lynch, AK., and Mills, K.V. (2022) Conditional Alternative Protein Splicing Promoted by Inteins from Haloquadratum walsbyi.  Biochemistry, 61, 294-302.

39. *Wall, D.A., *Tarrant, S.P., Wang, C., Mills, K.V., and Lennon, C.W. (2021) Intein Inhibitors as Novel Antimicrobials: Protein Splicing in Human Pathogens, Screening Methods, and Off-Target Considerations. Front. Mol. Biosci. 8, 752824, 1-17.

38. *Williams, J.E., *Jaramillo, M.V., Li, Z., Zhao, J., Wang, C., Li, H.,  and Mills, K.V. (2021) An alternative domain-swapped structure of the Pyrococcus horikoshii PolII mini-intein. Scientific Reports, 11, 11680, 1-12.

37. Robinzon, S., *Cawood, A.R., *Ruiz, M.A., Gophna, U., Altman-Price, N., and Mills, K.V. (2020) Protein Splicing Activity of the Haloferax volcanii PolB-c intein is sensitive to homing endonuclease domain mutations. Biochemistry, 59, 3359-3367.

36. *Chiarolanzio, K.C., *Pusztay, J.M., *Chavez, A., Zhao, J., Xie, J., Wang, C., and Mills, K.V. (2020) Allosteric Influence of Extremophile Hairpin Motif Mutations on the Protein Splicing Activity of a Hyperthermophilic Intein. Biochemistry, 59, 2459-2467.

35. Zhao, J., Du, Z., Wang, C., and Mills, K.V. (2020) Methods to Study the Structure and Catalytic Activity of cis-splicing Inteins. Methods Mol Biol, 2133, 55-73.

34. *Ramsoomair, C.K., *Yakely, A.E., *Urbanski, L.M., *Karanja, K., *Giaccone, Z.T., *Siegart, N.M., Wang, C., Gomez, A.V., Reitter, J.N., and Mills, K.V. (2017) Coordination of the third step of protein splicing in two cyanobacterial inteins. FEBS Letters, 591, 2147-2154.

33. Zwarycz, A.S., Fossat, M., Akanyeti, O., Lin, Z., Rosenman, D.J., Garcia, A., Royer, C.A., Mills, K.V., and Wang, C. (2017) V67L Mutation Fills Internal Cavity to Stabilize RecA Mtu Intein. Biochemistry 56, 2715-2722.

32.*Minteer, C.J., *Siegart, N.M., *Colelli, K.C., Liu, X., Linhardt, R.J., Wang, C., Gomez, A.O., Reitter, J.N., and Mills, K.V. (2017) Intein-promoted cyclization of aspartic acid flanking the intein leads to atypical C-terminal cleavage. Biochemistry 56, 1042-1050.

31. Reitter, J.N., *Cousin, C.E., *Nicastri, M.C., *Jaramillo, M.V., and Mills, K.V. (2016) Salt-dependent conditional protein splicing of an intein from Halobacterium salinarum. Biochemistry 55, 1279-1282.

30. Mills, K.V. (2015) Biochemistry in an undergraduate writing-intensive first-year program: Seminar courses in drugs and bioethics. Biochemistry and Molecular Biology Education 43, 263-272.

29. Kulevich, S.E., Herrick, R.S., and Mills, K.V. (2014) A Discovery Chemistry Experiment on Buffers. Journal of Chemical Education, J. Chem. Educ. 91, 1207-1211.

28. Mills, K.V., Johnson, M.A., and Perler, F.B. (2014) Protein splicing: How inteins escape from precursor proteins. Journal of Biological Chemistry, 289, 14498-14505.

27. Topilina, N.I. and Mills, K.V. (2014) Recent advances in in vivo applications of intein-mediated protein splicing. Mobile DNA 5, 5.

26. *Nicastri, M.C., *Xega, K., Li, L., Xie, J., Wang, C., Linhardt, R.J., Reitter, J.N., and Mills, K.V. (2013) Internal Disulfide Bond Acts as a Switch for Intein Activity. Biochemistry 52, 5920-5927.

25. Mills, K.V. (2013) Self-Splicing Proteins. In: Handbook of Proteolytic Enzymes, Third Edition, Vol. 1., ed. N. Rawlings and G. Salvesen, 315-321.

24. Chen, W., Li, L., Du, Z., Liu, J., Reitter, J.N., Mills, K.V., Linhardt, R.J. and Wang, C. (2012) Intramolecular Disulfide Bond between Catalytic Cysteines in an Intein Precursor. J. Am. Chem. Soc.,134, 2500-2503.

23. Du, Z., Liu, J., Albracht, C.D., Hsu, A., Chen, W., *Marieni, M.D., *Colelli, K.M., *Williams, J.E., Reitter, J.N., Mills, K.V. and Wang, C. (2011) Structural and Mutational Studies of a Hyperthermophilic Intein from DNA Polymerase II of Pyrococcus abyssi. J. Biol. Chem. 286, 38638-38648. (Cover of Nov. 4 2011 issue.)

22. Liu, J., Du, Z., Albracht, C.D., Naidu, R.O., Mills, K.V. and Wang, C. (2011) (1)H, (13)C, and (15)N NMR assignments of the Pyrococcus abyssi DNA Polymerase II intein. Biomol. NMR Assign. 5, 233-235.

21. Reitter, J.N. and Mills, K.V. (2011) Canonical protein splicing of a class one intein that has a class three non-canonical sequence motif. J. Bacteriol. 193, 994-997.

20. *O’Brien, K.M., *Schufreider, A.K., *McGill, M.A., *O’Brien, K.M., Reitter, J.N. and Mills, K.V. (2010) Mechanism of protein splicing of the Pyrococcus abyssi lon protease intein. Biochem. Biophys. Res. Commun.403, 457-461.

19. *Kerrigan, A.M, *Powers, T.L, *Dorval, D.M., Reitter, J.N. and Mills, K.V. (2009) Protein Splicing of the Three Pyrococcus abyssi ribonucleotide reductase inteins. Biochem. Biophys. Res. Commun. 387, 153-157.

18. Mills, K.V., Herrick, R.S., Ditzler, M.A., Nestor, L.P., Shafer, H., and Guilmette, L.W. (2008) Introducing Undergraduate Students to Electrochemistry: A Two-Week Discovery Chemistry Experiment. J. Chem. Educ.85, 1116-1119.

17.  Herrick, R.S., Mills, K.V., and Nestor, L.P. (2008) Data Pooling in a Chemical Kinetics Experiment: The Aquation of a Series of Cobalt (III) Complexes. J. Chem. Educ. 85, 1120-1122.

16.  Mills, K.V. and Guilmette, L.W. (2007) Thermochemical Analysis of Neutralization Reactions: An Introductory Discovery Experiment. J. Chem. Educ. 84, 326-328.

15.  Bellin, R.M. and Mills, K.V. (2007) The ������̳ Biochemistry Concentration: An Integrated Four-Year Program to Develop Undergraduate Research Scholars. In Developing and Sustaining a Research-Supportive Curriculum, ed K.K. Karukstis and T.E. Elgren, Council on Undergraduate Research.

14.  Mills, K.V., Connor, K.R., *Dorval, D.M., and *Lewandowski, K.T. (2006) Protein Purification via Temperature-Dependent, Intein-Mediated Cleavage from an Immobilized Metal Affinity Resin.  Anal. Biochem.356, 86-93.

13.  Mills, K.V., *Dorval, D.M., *Lewandowski, K.T. (2005) Kinetic analysis of the individual steps of protein splicing for the Pyrococcus abyssi PolII intein. J. Biol. Chem 280, 2714-2720.

12. Mills, K.V., *Gareau, J.R., and *Garcia, A.M. (2005) Low-cost modification to the Copacabana method for spreading transformation mixtures.  BioTechniques39, 188.

11. Mills, K.V., Perler, F.B. (2005) The Mechanism of Intein-Based Protein Splicing: Variations on a Theme.Protein & Peptide Letters, 12, 751-755.

10. Mills, K.V. (2005) Protein Splicing. In Encyclopedia of Molecular Cell Biology and Molecular Medicine,Second Edition, ed, RA Meyers, 241-265, Weinheim: Wiley-VCH. 

9. Mills, K.V., Paulus, H. (2005) Biochemical Mechanisms of Intein-Mediated Protein Splicing. In Nucleic Acids and Molecular Biology16 (Homing Endonucleases and Inteins), ed. M. Belfort, 231-255, Berlin: Springer Verlag.

8. Mills, K.V., *Manning, J.S., *Garcia, A.M., *Wuerdeman, L.A. (2004) Protein splicing of a Pyrococcus abyssiintein with a C-terminal glutamine.  J. Biol. Chem.279, 20685-20691.

7. Mills, K.V. (2004) Self-Splicing Proteins.  In: Handbook of Proteolytic Enzymes, Second Edition, Vol. 2., ed. AJ Barrett, 2136-2140, London: Academic Press, Elsevier Science.

6. Mills, KV.  (2003) Post-Translational Control.  In: Genetics, Vol. 3., ed. R Robinson, 178-182, New York: Macmillan Reference USA.

5. Mills, K.V., Paulus, H.  (2001) Reversible Inhibition of Protein Splicing by Zinc Ion.  J. Biol. Chem. 276, 10832-10838.

4. Lew, B.M., Mills, K.V., Paulus, H. (1999) Characteristics of Protein Splicing in trans Mediated by a Semisynthetic Split Intein. Biopolymers (Peptide Science)51, 355-362.

3. Lew, B.M., Mills, K.V., Paulus, H. (1998) Protein Splicing in Vitro with a Semisynthetic Two-Component Minimal Intein. J. Biol. Chem.273, 15887-15890.

2. Mills, K.V., Lew, B.M., Jiang, Sq, Paulus, H.  (1998) Protein splicing in trans by purified N- and C- terminal fragments of the Mycobacterium tuberculosis RecA intein. Proceedings of the National Academy of Sciences, USA95, 3543-3548.

1. Broomfield, C.A., Mills, K.V., Meier, B.M., Lockridge, O.A., and Millard, C.B.  (1998) Reaction of human butyrylcholinesterase (BchE) H117 enzymes with carbamates.  In: Structure and Function of Cholinesterases and Related Proteins, 223-226.

2024-2027     National Institutes of Health, NIGMS, R15: "The Regulation of Inteins: Adaptations to Extreme Environments and Targets for Drug Discovery"

2022-2024     Research Corporation for Science Advancement, SEED (Singular Exceptional Endeavors of Discovery: "Folding Inhibitors of Inteins: a novel drug target."

2019-2023     National Institutes of Health, NIGMS, R15: "Conditional Protein Splicing of inteins from extreme thermophiles and halophiles: Structure, Mechanism, and Function."

2015-2019      National Science Foundation, RUI: "RUI: The Catalysis of Protein Splicing and the Structure and Stability of Thermophilic Inteins: An Integrated Research and Education Program"

2015                Research Corporation Cottrell Scholar
 

2013-2016      National Science Foundation, RUI: "Intein Structure and Catalysis of Protein Splicing and Hedgehog Autoprocessing: An Integrated Research and Education Program"

2010-2013      National Science Foundation, RUI: "Catalysis and coordination of the steps of protein splicing by non-canonical inteins: An integrated research and education program"
 

2009-2014      Henry Dreyfus Teacher-Scholar Award
 

2009                ASBMB-UAN Outreach Award
 

2005-2010      National Science Foundation, CAREER grant, “CAREER: Alternative Mechanisms of HINT domain autoprocessing: An integrated undergraduate research and education program”
 

2003-2005      National Science Foundation, Major Research Instrumentation, “Acquisition of Protein Purification and Analysis Equipment to Enhance Biochemical Research and Education at the Holy Cross� 
 

2003-2005      Research Corporation, Cottrell College Science Award, “The Mechanism and Molecular Evolution of Hedgehog Proteins and Related Auto-Processing Domains”
 

2002-2004      Petroleum Research Fund (American Chemical Society), Type GB, “The Mechanism of Protein Splicing and the Molecular Evolution of Inteins.”
 

1997-2001      Howard Hughes Medical Institute Predoctoral Fellowship
 

1995-1996      Barry M. Goldwater Fellowship

Our lab studies protein splicing and the enzymology of extreme thermophiles.

Protein splicing is a post-translational modification. It involves the self-catalyzed excision of an intervening polypeptide sequence, the intein, concomitant to the ligation of the flanking polypeptides, the exteins, via a native peptide bond.

We are interested in:

a) The means by which non-canonical inteins facilitate the individual steps of protein splicing.

b) The means by which inteins coordinate the steps of splicing.

c) The role that inteins play in the control of extein function.

d) What are the potential role of inteins for the host.

e) Comparisons of the catalytic strategies of enzymes from halophiles, thermophiles, and other extremophiles and their mesophilic equivalents.